The tumor cell plasma membrane is clearly the primary interface for host-tumor interactions. A greater knowledge of the dynamics and nature of this structure would significantly enhance understanding of the host response to tumor and the nature of tumor cell-host cell interactions. Cell surface molecules encoded by genes within the major histocompatibility complex (the MHC antigens) are known to perform essential functions in the initiation, developments, and culmination of the immune response. Recent findings indicate that some tumor cells express MHC antigens which are quantitatively and/or qualitatively distinct from those expressed on their normal cell counterparts. Clearly such changes in tumor cell phenotype could have pronounced effects on the generation and outcome of the host immune response and host-tumor interactions in general. This project is designed to investigate the nature, source, and mechanism of action of host-derived soluble factors (distinct from interferons) which effect the class II HMC antigen phenotype of tumor cells. In addition, the chemistry of induced class II antigens will be investigated and the effects of these molecules on the host antitumor immune response will be examined. Furthermore, experimentation will be performed to investigate the direct effects of the host immune response on the class I MHC antigen phenotype of tumor cells. Tumor cell variants will be selected for using immune T cells. The MHC antigens of these variants will be characterized to determine if class I MHC antigen variants arise as a result of the selective pressures exerted by the host immune response. Finally, the effects of changes in the class I MHC antigens of thes tumor cells on host-tumor interactions (particularly the host antitumor immune response and the process of tumorigenesis) will be thoroughly characterized. These combined studies are designed to provide essential information about MHC antigen expression by tumor cells and the effects of changes in the expression of the cell surface glycoprateins on the host immune response and the process of tumorigenesis.